- Structural optimization of natural product nordihydroguaretic acid to discover novel analogues as AcrB inhibitors
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Drug efflux pumps confer multidrug resistance to dangerous bacterial pathogens which makes these proteins promising drug targets. Herein, we present initial chemical optimization and structure-activity relationship (SAR) data around a previously described efflux pump inhibitor, nordihydroguaretic acid (NDGA). Four series of novel NDGA analogues that target Escherichia coli AcrB were designed, synthesized and evaluated for their ability to potentiate the activity of antibiotics, to inhibit AcrB-mediated substrate efflux and reduce off-target activity. Nine novel structures were identified that increased the efficacy of a panel of antibiotics, inhibited drug efflux and reduced permeabilization of the bacterial outer and inner membranes. Among them, WA7, WB11 and WD6 possessing broad-spectrum antimicrobial sensitization activity were identified as NDGA analogues with favorable properties as potential AcrB inhibitors, demonstrating moderate improvement in potency as compared to NDGA. In particular, WD6 was the most broadly active analogue improving the activity of all four classes of antibacterials tested.
- Alenzy, Rawaf,Liu, Xingbang,Ma, Shutao,Ma, Yingang,Mowla, Rumana,Polyak, Steven W.,Song, Di,Teng, Yuetai,Venter, Henrietta,Wang, Yinhu
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- Dihedral-Angle-Controlled Crossover from Static Hole Delocalization to Dynamic Hopping in Biaryl Cation Radicals
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In cases of coherent charge-transfer mechanism in biaryl compounds the rates follow a squared cosine trend with varying dihedral angle. Herein we demonstrate using a series of biaryl cation radicals with varying dihedral angles that the hole stabilization
- Talipov, Marat R.,Navale, Tushar S.,Hossain, Mohammad M.,Shukla, Ruchi,Ivanov, Maxim V.,Rathore, Rajendra
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supporting information
p. 266 - 269
(2016/12/30)
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- Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents
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Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in L
- Vijaya Bhaskar Reddy, Mopur,Hung, Hsin-Yi,Kuo, Ping-Chung,Huang, Guan-Jhong,Chan, Yu-Yi,Huang, Shiow-Chyn,Wu, Shwu-Jen,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung,Wu, Tian-Shung
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p. 1547 - 1550
(2017/03/17)
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- Domino Reactions Containing Different Types of Heck Reactions for Selective 3,3- and 1,3-Diarylations of Propenol with Aryl Halides by Triple Catalysis
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A new domino Heck-isomerization/Saegusa/Heck reaction of propenol with aryl iodides has been developed for the synthesis of 3,3-diaryl propenals by triple transition-metal catalysis. Moreover, we also developed the domino Heck-isomerization/Heck-type reaction of propenol with aryl iodides for the synthesis of 1,3-diaryl propanones by double transition-metal catalysis and the mediation of secondary amine or triple transition metal catalysis and aminocatalysis.
- Zhu, Zhi-Qiang,He, Jian-Shi,Wang, Hai-Jun,Huang, Zhi-Zhen
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p. 9354 - 9359
(2015/09/28)
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